Evaluation of Dupilumab in Patients With Severe Steroid Dependent Asthma

A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Dupilumab in Patients With Severe Steroid Dependent Asthma

Primary Objective:

To evaluate the efficacy of dupilumab, compared with placebo, for reducing the use of maintenance oral corticosteroids (OCS) in participants with severe steroid-dependent asthma.

Secondary Objectives:

• To evaluate the safety and tolerability of dupilumab.
• To evaluate the effect of dupilumab in improving participants-reported outcomes.
• To evaluate dupilumab systemic exposure and the incidence of treatment-emergent antidrug antibodies.

The total study duration per participant was up to 46 weeks, consisting of a screening period of 3 to up to 8 weeks (up to 10 weeks for participants who experienced a clinically significant asthma exacerbation during the screening period), a randomized treatment period of up to 24 weeks, and a post-treatment period of 12 weeks.

Participants who completed treatment were considered for eligibility into the long term extension study LTS12551 (NCT02134028).

Inclusion criteria :

Adult and adolescent (12 years of age or older) participants with a physician diagnosis of asthma for >=12 months, based on the Global Initiative for Asthma (GINA) 2014 guidelines and the following criteria:

• Participants with severe asthma and a well-documented, regular prescribed treatment of maintenance corticosteroids in the 6 months prior to Visit 1 and using a stable OCS dose (ie, no change of OCS dose) for 4 weeks prior to Visit 1. Participants must be taking 5 to 35 mg/day of prednisone/prednisolone, or the equivalent, at Visit 1 and at the randomization visit. In addition, the participants must agree to switch to study-required prednisone/prednisolone as their OCS and use it per protocol for the duration of the study.
• Existing treatment with high-dose inhaled corticosteroid (ICS; >500 mcg total daily dose of fluticasone propionate or equivalent) in combination with a second controller (ie, long-acting beta agonist [LABA], leukotriene receptor antagonist [LTRA]) for at least 3 months with a stable dose of ICS for >=1 month prior to Visit 1. In addition, participants requiring a third controller for their asthma are considered eligible for this study, and it should also be used for at least 3 months with a stable dose >= 1 month prior to Visit 1.
• A forced expiratory volume in 1 second (FEV1) <80% of predicted normal for adults and <=90% of predicted normal for adolescents at Visit 1.
• Evidence of asthma as documented by either: reversibility of at least 12% and 200 mL in FEV1 after the administration of 200 to 400 mcg (2 to 4 inhalations of albuterol/salbutamol or levalbuterol/levosalbutamol, or of a nebulized solution of albuterol/salbutamol or levalbuterol/levosalbutamol, if considered as a standard office practice) before randomization or documented in the 12 months prior to Visit 1 OR airway hyperresponsiveness (methacholine: provocative concentration that causes a positive reaction [PC20] of <8 mg/mL) documented in the 12 months prior to Visit 1.

Exclusion criteria:

• Participants <12 years of age or the minimum legal age for adolescents in the country of the investigative site, whichever is higher (for those countries where local regulations permit enrollment of adults only, participant recruitment will be restricted to those who were >=18 years of age).
• Participants who weighed <30.0 kg.
• Chronic obstructive pulmonary disease (COPD) or other lung diseases (eg, idiopathic pulmonary fibrosis, Churg-Strauss Syndrome, allergic bronchopulmonary aspergillosis, cystic fibrosis) which may impair lung function.
• Clinical evidence or imaging (eg, chest X-ray, computed tomography, magnetic resonance imaging) within 12 months of Visit 1 with clinically significant findings of lung disease(s) other than asthma, as per local standard of care.
• A participant who experiences a deterioration of asthma that results in emergency treatment or hospitalization within 4 weeks of Screening Visit 1.
• A participant who requires 12 puffs or more of rescue medication on any 1 day in the week prior to Visit 1.
• A participant who has experienced an upper or lower respiratory tract infection within the 4 weeks prior to screening.
• Current smoker or cessation of smoking within 6 months prior to Visit 1.
• Previous smoker with a smoking history >10 pack-years.
• Comorbid disease that might interfere with the evaluation of the investigational medicinal product.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.